Inside Health

Cocaine Use Tied to Loss of Pleasure Sense

Published: January 7, 2003

Chronic cocaine use harms brain circuits that help produce the sense of pleasure, in part explaining why cocaine addicts have a higher rate of depression, a study suggests.

It is not clear whether cocaine kills brain cells or merely impairs them, or whether the effect is reversible, said the author of the study, Dr. Karley Little.

But it is bad news in any case for people addicted to cocaine, he said.

''I personally wouldn't want to lose 10 or 20 percent of my reward-pleasure center neurons, or have them just deranged or not working right,'' said Dr. Little of the University of Michigan and the Veterans Affairs Medical Center in Ann Arbor.

He and colleagues studied brain samples taken during autopsies from long-term, heavy cocaine users. Their results were reported this month in The American Journal of Psychiatry.

Dr. Little said the research did not reveal whether the brain impairment resulted from years of use or just recent use before death.

Dr. Stephen Kish, head of the human brain laboratory at the Center for Addiction and Mental Health in Toronto, said researchers had ''always considered cocaine to be a dangerous drug'' because of its potential for addiction and its harm to the heart.

Dr. Kish said they could now add to the list of risks ''a damaging effect of cocaine on the brain, which was something we never expected before.''

The research provides ''a piece of the puzzle'' in explaining why cocaine users run a higher risk of depression, said Dr. Deborah Mash, a neuroscientist at the University of Miami School of Medicine.

It remains unclear whether cocaine causes depression or whether people start using the drug because they are depressed. But in either case, Dr. Mash said, the study suggests that brain changes may ''light the fuse'' for depression in a cocaine user who is prone to it.

The study also suggests that the brain changes may cause the depression commonly seen in cocaine withdrawal, Dr. Mash said.

In the study, Dr. Little and colleagues studied brain autopsy specimens from an area called the striatum in 35 cocaine users and 35 nonusers of similar age and sex.

They measured levels of a protein called VMAT2, which is found in brain cells that signal one another with a chemical called dopamine. Dopamine neurons form circuits that are critical for the brain to feel pleasure.

The study found that cocaine users' VMAT2 levels were lower on average. That could mean that dopamine neurons had been damaged or killed -- an effect not observed in animal studies -- or that they were making less VMAT2, which suggests they also were making less dopamine, Dr. Little said.

A person with impaired or missing dopamine neurons could have difficulty feeling pleasure and might become depressed, said Dr. Little, who added that researchers would now compare the number of dopamine neurons in the autopsy specimens.

The study found hints that VMAT2 levels were lower in cocaine users with severe depression than in other users, but statistical analysis suggested this could be a coincidence. Dr. Little said the link was strengthened when other data were taken into account.